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Review
. 2017:2017:3264217.
doi: 10.1155/2017/3264217. Epub 2017 Aug 1.

Advances in Immunotherapy for Melanoma: A Comprehensive Review

Carmen Rodríguez-Cerdeira  1 , Miguel Carnero Gregorio  2 , Adriana López-Barcenas  3 , Elena Sánchez-Blanco  4 , Beatriz Sánchez-Blanco  5 , Gabriella Fabbrocini  6 , Brunilda Bardhi  7 , Ardiana Sinani  8 , Roberto Arenas Guzman  3
Affiliations
Review

Advances in Immunotherapy for Melanoma: A Comprehensive Review

Carmen Rodríguez-Cerdeira et al. Mediators Inflamm. 2017.

Abstract

Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific focus on the identification of neoantigens for the prediction of their elicited immune responses. This review is expected to provide important insights into the future of immunotherapy for melanoma.

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Figures

Figure 1
Figure 1
Schematic of the multitude of interacting genetic factors that influence the pathogenesis of melanoma. Oncogenic NRAS mutations activate the effector pathways PI3K-AKT and Raf-MEK-ERK. The latter pathway is also activated by means of mutations in the BRAF gene. In contrast, PI3K-AKT pathway activation is conditioned by the loss or mutation of the tumor suppressor gene PTEN. These changes are generally preserved throughout tumor progression. The development of melanoma has been shown to be strongly associated with the inactivation of the tumor suppressors p16INK4a/cyclin-dependent protein kinases 4 and 6/retinoblastoma (p16INK4a/CDK4,6/pRb) and p14ARF/human double minute 2/p53 (p14ARF/HMD2/P53). Other factors such as microphthalmia-associated transcription factor (MITF) and TP53 play a crucial role in the progression of melanoma [4].
Figure 2
Figure 2
Control of checkpoint blockade and targeted therapy in metastatic melanoma. Four steps are required to attack the tumor cell by the immune system: recognition, tumor antigen presentation to T cells, T cell activation, and direct tumor attack. MHC: major histocompatibility complex; TCR: T cell receptor; CTLA-4: cytotoxic T-lymphocyte antigen 4.
Figure 3
Figure 3
Different vehicles could bind to tumor antigens and adjuvants resulting in antigen-presenting to dendritic cells (DCs). Once these vehicles are absorbed, both the antigen and the adjuvant will be released and degraded, leading to acceleration of the maturation of DCs as well as MHC molecules located on the cell surface that present the antigen. This will allow binding to CD8+ T cells that are activated, proliferated, and generated an antitumor response. MC: major histocompatibility complex; TCR: T cell receptor.
Figure 4
Figure 4
Dendritic cells regulating Th1 and Th2 development in melanoma (modified from the BioCarta database) [29].
Figure 5
Figure 5
T cell receptor (TCR) signaling pathway in melanoma (modified from the BioCarta database) [29].
See this image and copyright information in PMC

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